p53 modulation of Fas/Apo-1 mediated apoptosis in a human renal cell carcinoma cell line.
The mutant p53 gene was transfected into ACHN, a wild-type p53-containing human renal cell carcinoma (RCC) cell line. The colony forming efficiency in soft agar in the mutant-type p53-transfected cell line (ACHN/MP) was significantly higher than that in the vector-only transfected control cell line (ACHN/C). The anti-Fas monoclonal antibody (CH11) induced apoptosis in the ACHN/C cells in a dose-dependent manner, whereas the effect of CH11 on the ACHN/ MP cells was markedly suppressed. In addition, the cytotoxic effect of CH11 on the ACHN/MP cells was augmented by the pretreatment with interferon- , but the corresponding effect on ACHN/C cells was not. These findings suggest that Fas-mediated therapy could be a novel approach to RCC, if interferon- treatment is added according to the p53 gene status.
Miyake
H
H
Department of Urology, Kobe University School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650, Japan.
Hara
I
I
Gohji
K
K
Arakawa
S
S
Kamidono
S
S
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D015153:Blotting, Western; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000473:pathology*; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D007680:Kidney Neoplasms / Q000235:genetics / Q000473:pathology*; D009154:Mutation; D014162:Transfection; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000276:immunology / Q000502:physiology*
D000911:Antibodies, Monoclonal; D016898:Interferon-alpha; D007376:Interleukin-2; D019014:fas Receptor; D007371:Interferon-gamma